Endovascular therapy of acute ischemic stroke: report of the … · Endovascular therapy of acute ischemic stroke: report of the Standards of Practice Committee of the Society of

Endovascular therapy of acute ischemic stroke: reportof the Standards of Practice Committee of the Societyof NeuroInterventional Surgery

K A Blackham,1 P M Meyers,2 T A Abruzzo,3 F C Alberquerque,4 D Fiorella,5

J Fraser,6 D Frei,7 C D Gandhi,8 D V Heck,9 J A Hirsch,10 D P Hsu,1 M Jayaraman,11

S Narayanan,12 C Prestigiacomo,13 J L Sunshine,1 on behalf of the Society forNeuroInterventional Surgery

ABSTRACTObjective To summarize and classify the evidence for theuse of endovascular techniques in the treatment ofpatients with acute ischemic stroke.Methods Recommendations previously published by theAmerican Heart Association (AHA) (Guidelines for theearly management of adults with ischemic stroke(Circulation 2007) and Scientific statement indicationsfor the performance of intracranial endovascularneurointerventional procedures (Circulation 2009)) werevetted and used as a foundation for the current process.Building on this foundation, a critical review of theliterature was performed to evaluate evidence supportingthe endovascular treatment of acute ischemic stroke.The assessment was based on guidelines for evidencebased medicine proposed by the Stroke Council of theAHA and the University of Oxford, Centre for EvidenceBased Medicine (CEBM). Procedural safety, technicalefficacy and impact on patient outcomes werespecifically examined.

RECOMMENDATIONS1. The availability of intra-arterial therapy should

generally not preclude the intravenous adminis-tration of recombinant tissue plasminogenactivator (rt-PA) in otherwise eligible patients(American Heart Association (AHA) Class I,Level of Evidence A, Centre for Evidence BasedMedicine (CEBM) level 1b, grade AeB).*

2. Treatment requires the patient to be at anexperienced stroke center with rapid access tocerebral angiography and qualified intervention-alists (AHA Class I, Level of Evidence C, CEBMlevel 2C, grade C).*

3. Intra-arterial chemical thrombolysis is an optionfor the treatment of selected patients withmajor stroke of <6 h duration due to anocclusion of the middle cerebral artery andwho are not otherwise candidates for intrave-nous rt-PA (AHA Class I, Level of Evidence B,CEBM level 2b, grade B).*

4. Intra-arterial chemical thrombolysis is reason-able for patients who have contraindications tothe use of intravenous thrombolysis, such asrecent surgery (AHA Class IIa, Level of EvidenceC, CEBM level 4, grade C).*

5. Combination intravenous/intra-arterial therapyis reasonable in selected patients who present

with major stroke of <4.5 h duration (AHAClass IIa, Level of Evidence B, CEBM level 2a,grade B).

6. Intra-arterial thrombus removal with thePenumbra aspiration system or ConcentricMERCI clot retrieval device is reasonable inselected patients with major stroke where carehas been initiated at <8 h duration althoughdata regarding improvement of clinicaloutcomes is unclear (AHA Class IIa, Level ofEvidence B, CEBM level 2a, grade B).

7. The usefulness of other endovascular devices isnot yet established, but they may be beneficialand may be considered (AHA Class IIb, Level ofEvidence C, CEBM level 4, grade C.)*

8. The usefulness of endovascular treatment in theposterior circulation is not yet established, but itmay be beneficial and may be considered, evenbeyond the 6e8 h time window typical foranterior circulation stroke (AHA Class IIB, Levelof Evidence C).

*As already defined by the AHA guidelines forthe early management of adults with ischemicstroke (Circulation 2007) and AHA statementregarding indications for the performance of intra-cranial endovascular neurointerventional procedures(Circulation 2009).1 2

INTRODUCTIONStroke is the third leading cause of death in theUSA, Canada, Europe and Japan. According to theAmerican Heart Association (AHA) and the Amer-ican Stroke Association, there are now 795 000 newstrokes that occur each year, resulting in 200 000deaths, or 1 of every 16 deaths, per year in the USAalone.3 Ischemic stroke accounts for more than 80%of the total while hemorrhagic stroke accounts forthe remainder. Stroke is the leading cause of adultdisability in North America4 and the primary causefor inpatient Medicare reimbursement for longterm adult care.5 6 The National Institutes ofHealth estimates that stroke costs now exceed $62billion in US healthcare dollars per year.7 There arevarying estimates as to potential numbers ofischemic stroke patients that might benefit fromendovascular therapy but many expect an expan-sion of the number of patients treated with thesetechniques.8 9

The purpose of this document is to define theexisting scientific basis for endovascular acute

For numbered affiliations seeend of article.

Correspondence toDr K A Blackham, Departmentof Radiology, UniversityHospitals of Cleveland, CaseWestern Reserve University,11100 Euclid Ave, Cleveland,OH 44106, USA; [email protected]

Accepted 20 December 2011Published Online First24 January 2012

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ischemic stroke (AIS) treatment. The discussion of whatconstitutes adequate training and experience in endovascularsurgical neuroradiology, both cognitive and technical, has beenpublished elsewhere.10 In addition, national professional orga-nizations have published performance and training standards forcervicocerebral angiography.11 12 Quality improvement guide-lines for adult diagnostic cervicocerebral angiography have alsobeen formally adopted by professional specialty societies.13

Adherence to these standards and guidelines is a prerequisite andfundamental for any interventional stroke treatment procedure.

Guidelines for performance of endovascular ischemic stroketherapy represent a multidisciplinary effort to reduce death anddisability from this condition. These guidelines intend toencompass the training and experience of all physicians involvedin the care of patients with cervicocerebral vascular diseaseregardless of medical specialty. In developing the presentrecommendations, the writing group conducted a systematicreview of English language literature published between January1998 and January 2011 to evaluate the evidence supporting theendovascular treatment of AIS, as well as incorporating alreadyexisting guidelines published by the AHA.1 2 The writing grouphas applied the rules of evidence14 and formulation of strengthof recommendations used by other AHA guideline panels, andby the University of Oxford, Center for Evidence Based Medi-cine (CEBM).15e17 Procedural safety, technical efficacy andimpact on patient outcomes were specifically examined.

Endovascular therapy for patients with AIS is an area ofintense investigation and brisk technological development. This,in combination with the fact that the outcome of AIS maydepend on numerous variables, such as thrombus type, locationand clot burden, individual patient parameters like age, collateralcirculation and underlying comorbidities, as well as time totreatment, unfortunately restricts the availability of standard-ized outcomes research. Intra-arterial (IA) thrombolysis has beenstudied in two randomized trials18 19 and numerous case seriesand is endorsed by national organizations as an acceptablealternative stroke therapy, in selected patients. In the pastdecade, two devices received Food and Drug Administration(FDA) approval for safety and efficacy in endovascular thrombusremoval.20 21 Several other devices, drugs and other reperfusionstrategies are used off-label or are in development with the goalof obtaining the most rapid and complete recanalizationpossible, while minimizing vascular damage and hemorrhagiccomplications.

INTRAVENOUS THROMBOLYSISThe availability of intra-arterial therapy should not preclude theintravenous administration of recombinant tissue plasminogen acti-vator (rt-PA) in otherwise eligible patients (AHA Class I, Level ofEvidence A, CEBM level 1b, grade AeB).

At present, the only therapy demonstrated to improve clinicaloutcomes from AIS in randomized controlled clinical trials isthrombolysis of the clot responsible for the ischemic event.22e25

Specifically, since 1996, intravenous (IV) thrombolysis withrecombinant tissue plasminogen activator (rt-PA) is FDAapproved for the treatment of ischemic stroke to patientswithout evidence of hemorrhage seen on initial non-contrasthead CT, if treatment is initiated within 3 h of a clearly definedsymptom onset. A 2009 scientific advisory from the AHA/American Stroke Association26 recommended extension of thetime window for treatment with IV rt-PA to 4.5 h, largely basedon the prospective, randomized, placebo controlled EuropeanCo-operative Acute Stroke Study III (ECASS III) trial.23 rt-PA is

administered intravenously at a dose of 0.9 mg/kg (maximum of90 mg) with 10% of the total dose given as a bolus with theremainder infused over 60 min.26 27 This dosage has beenshown to be safe and effective in routine clinical use, withresults comparable with pooled, randomized, controlled trialdata in the Safe Implementation of Thrombolysis in StrokedMonitoring Study (SITS-MOST), a large observationalregistry.28 As noted below in the section on combinationtherapy (IV plus IA rt-PA), several trials and case series haveshown that patients with a large clot burden are not likely toachieve recanalization with IV rt-PA. A 2011 retrospectivereview of 138 patient treated with IV rt-PA demonstrated thatof the 76 patients who did not achieve recanalization, themajority had clot lengths which exceeded 8 mm. Clot lengthwas determined via automated measurements of vascularhyperdensity on thin section pretreatment CT scans. Theremaining patients who did achieve recanalization had clotlengths of <8 mm.29

ENDOVASCULAR TREATMENTTreatment requires the patient to be at an experienced stroke centerwith rapid access to cerebral angiography and qualified intervention-alists (AHA Class I, Level of Evidence C, CEBM level 2c, grade C).Endovascular treatment of stroke requires the infrastructure

to support the rapid assessment, stabilization and transport ofpatients with AIS, along with documented procedures forcommunication with the receiving hospital emergency roomand stroke team. Evaluation of the patient before and after theprocedure requires a multidisciplinary team approach not onlyfor discussion of endovascular treatment options, particularly onfull evaluation of the underlying vascular disease, but also forevaluation and treatment of the attendant complications.Nursing and technological staff should have training in endo-vascular procedures and should be available on a continuousbasis with a 60 min response time to the hospital. There shouldbe documentation and evaluation of procedural indications,outcomes and complications with the support of a qualityassurance program. This brief description of an experiencedstroke center is subsumed within the more detailed evidencebased guidelines describing the concept of a ComprehensiveStroke Center (CSC), defined by the Brain Attack Coalition in2005 as a facility or system that is able to “diagnose and treatstroke patients who require a high intensity of medical andsurgical care, specialized tests or interventional therapies”.30 TheCSC is the highest level of stroke care within the auspices oflarger ‘stroke systems of care’, as advocated by the AmericanStroke Association.31

A Center for Disease Control and Prevention evaluation ofdata from the 2005e2007 Paul Coverdell National Acute StrokeRegistry recommends that coordinated stroke programs andsurveillance of performance measures are needed in order toimprove adherence to measures that improve the stroke qualityof care.32 The ‘Get With The Guidelines’ stroke program of theAHA is a national stroke quality improvement program devel-oped to reduce disparities in acute stroke care. Voluntary coop-eration with this program is associated with substantial andsustained improvement in hospital based acute stroke careregardless of hospital size, geography and teaching status.33

Since the original publication of Primary Stroke Center recom-mendations in 2000, there have been over 800 facilities certifiedby the Joint Commission and improved outcomes have beenvalidated by several studies evaluating the stroke systems ofcare.34

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INTRA-ARTERIAL THROMBOLYSISIntra-arterial thrombolysis is indicated for the treatment of selectedpatients with major stroke of <6 h duration due to an occlusion of themiddle cerebral artery (AHA Class I, Level of Evidence B, CEBM level2b, grade B).

Intra-arterial thrombolysis is reasonable for patients who havecontraindications to the use of intravenous thrombolysis, such as recentsurgery (AHA Class IIa, Level of Evidence C, CEBM level 4, grade C).

IA thrombolysis provides a supplement or alternative to IVthrombolysis in carefully selected patients with AIS. Delivery offibrinolytic agents directly into the thrombus permits adminis-tration of a smaller dose of the agent, which theoreticallydecreases the risk of cerebral and systemic hemorrhagiccomplications from systemic effects.35 This concept led tostudies that were designed to explore an extension of thetreatment window beyond the relatively short therapeuticwindow for IV rt-PA. Two randomized, multicenter, controlledtrials of IA thrombolysis in acute middle cerebral artery strokehave been completeddthe Prolyse in Acute Cerebral Thrombo-embolism Trial I (PROACT-I)18 and PROACT-II.19 Recanaliza-tion efficacy and safety of IA recombinant pro-urokinase(r-proUK) for middle cerebral artery occlusion of 6 h durationwas demonstrated in the PROACT-I trial. PROACT-II demon-strated a 15% absolute increase in good outcome. The results ofPROACT-II, although encouraging, were insufficient to secureFDA approval of r-proUK for an acute stroke indication. For thisreason, IA thrombolysis using any thrombolytic agent stillrepresents an ‘off-label’ use of r-proUK or rt-PA. The clinicalbenefits observed in the PROACT II study were confirmed ina recent meta-analysis of five randomized IA therapy trials,which included PROACT I, and the prematurely halted JapaneseMiddle Cerebral Artery Embolism Local Fibrinolytic Interven-tion Trial (MELT) trial, which also found higher rates of goodand excellent clinical outcomes in patients undergoing IAtherapy.36 In addition, several studies have suggested thatsuccessful recanalization correlates with improved clinicaloutcomes in patients with AIS secondary to large vessel occlu-sion.37 38 Retrospective studies have shown that IA thrombol-ysis within 3 h is possible at experienced stroke centers and doesnot significantly increase risk in patients who have contraindi-cations to IV thrombolysis, such as recent surgery.39e41 TheAHA/American Stroke Association Council endorses IA throm-bolysis as an acceptable stroke therapy in major stroke of <6 hduration due to an occlusion of the middle cerebral artery inpatients ineligible for IV thrombolysis.1 2

COMBINATION TREATMENTCombination intravenous/intra-arterial therapy is reasonable inselected patients who present with major stroke of <4.5 h duration(AHA Class IIa, Level of Evidence B, CEBM level 2a, grade B).

IV thrombolysis has the advantage of ease and efficiency ofadministration while IA thrombolysis has the potential forsuperior recanalization, particularly in proximal occlusions.Combining the two techniques was studied in the 1999 Emer-gency Management of Stroke (EMS) Bridging Trial42 and theInterventional Management of Stroke (IMS) studies I and II,published in 2004 and 2007, respectively.43 44 The results of IMSII confirmed the safety and increased recanalization ratesinitially observed in the EMS bridging trial. In IMS I, patientswere administered two-thirds dose IV rt-PA followed by IA rt-PAadministration. This approach yielded favorable outcomes in33% of subjects which was significantly greater than theoutcome of the historical control group (the placebo arm from

the National Institute of Neurological Disorders and Stroke(NINDS) trial) but not significantly different from the historicalpurely IV thrombolysis group. Both IMS I and II found that IVtherapy alone rarely achieved recanalization of large vesselocclusion. Several case series have supported these findings.45e47

Currently, a larger phase III, randomized, controlled IMS III trialis comparing the combined IV/IA approach to standard IV rt-PAtherapy alone. Due to the intervening development and FDAclearance of new devices, IA treatment in IMS III allows the useof the EKOS ultrasound microcatheter (which was used toaugment thrombus fragmentation in IMS II), the Penumbrathrombo-aspiration system as well as the Concentric MERCIclot retriever device. A recent meta-analysis investigated the useof IA thrombolysis after full dose IV tPA (0.9 mg/kg) andsuggested that this method of combined treatment is safe andassociated with higher recanalization rates and better functionaloutcome at 3 months.48

ENDOVASCULAR THROMBUS REMOVALIntra-arterial thrombus removal with the Penumbra aspiration systemor Concentric MERCI device is reasonable in selected patients withmajor stroke where care has been initiated at <8 h duration althoughdata regarding improvement of clinical outcomes is unclear (AHAClass IIa, Level of Evidence B, CEBM level 2a, grade B).Rapid clot extraction enabling prompt cerebral reperfusion

has obvious appeal as a technique for ischemic stroke treatment.This treatment is theoretically ideal for those occlusions ofcardioembolic origin, with well organized platelet poorthrombus and extensive fibrin cross linking that is refractory tochemical lysis. The two FDA cleared devices for endovascularclot removal are the MERCI Retrieval System (ConcentricMedical Inc, Mountain View, California, USA) and thePenumbra stroke system (Penumbra Inc, Alameda, California,USA). The MERCI device was specifically designed and testedfor extracting clots from major cerebral arteries, such as thedistal internal carotid artery, the M1 segment of the middlecerebral and the vertebrobasilar arteries. Clots located in moredistal cerebral arteries, like the posterior cerebral arteries, distalsegments of the middle cerebral arteries or the anterior cerebralarteries are usually not accessible with the MERCI device andthe risks of aggressive distal cerebrovascular instrumentationmay not be justified by the potential clinical benefit. The safetyand efficacy of the MERCI retrieval device for thrombusretrieval was tested in two prospective, single arm, multicentertrials conducted in the USA and led to FDA approval for clotretrieval in the presence of acute stroke.49 However, theapproval has been criticized by stroke specialists because neitherof the two conducted clinical trials evaluating the MERCIretrieval device were designed to prove its clinical efficacy forstroke therapy.50 Similarly, the Penumbra pivotal trial wasa prospective, single cohort, phase 2 study to evaluate the safetyand effectiveness of the Penumbra system aspiration catheter in125 patients with moderate to severe acute stroke due to largevessel occlusion. The FDA approved Penumbra system is anaspiration catheter with a clot separator wire. While the studyresults showed an unusually high rate of recanalization, only25% of patients had a good 90 day clinical outcome as definedby a modified Rankin Scale score of #2, an outcome that is nobetter than the natural history of untreated acute strokepatients.21 Subsequent pooled analysis of the MERCI data,however, found that target vessel recanalization was thestrongest predictor of outcomes,51 which corroborates findingsin IMS I and II.


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OTHER ENDOVASCULAR APPROACHESThe usefulness of other endovascular devices is not yet established, butthey may be beneficial and may be considered (AHA Class IIb, Level ofEvidence C, CEBM level 4, grade C.)

Angioplasty alone and stent assisted angioplasty have beendescribed, in retrospective series, for the past decade in thetreatment of acute cerebral stroke, more recently using existingself-expanding stents approved for stent assisted coil emboli-zation and intracranial atherosclerosis.52e55 Despite a relativelyhigh technical success rate, there are potential immediate anddelayed complications of permanent stent placement in acutestroke. The additional risk of hemorrhagic stroke trans-formation with ongoing antiplatelet therapy is not welldefined. Likewise, the incidence of in-stent restenosis, whichaffects at least 30% of cerebral arteries stented for intracranialatherosclerosis, is not known for intracranial stents implantedfor recanalization of acute thrombus.56 A single arm, prospec-tive, FDA approved trial, Stent Assisted Recanalization in AcuteStroke (SARIS), reported data in 20 patients that supports therelative safety and angiographic efficacy of primary stenting inacute stroke.57 Closed cell stent designs allow for resheathing ofself-expanding stents, after partial or even full deployment,resulting in a retrievable stent that functions to restore flowtemporarily.58 While this may represent a new direction foracute stroke intervention, the concurrent use of anticoagulant,antiaggregating and thrombolytic medications requires fur-ther investigation before the routine implementation of thistreatment strategy.

POSTERIOR CIRCULATIONThe usefulness of endovascular treatment in the posterior circulation isnot yet established, but it may be beneficial and may be considered,even beyond the 6e8 h time window typical for anterior circulationstroke (AHA Class IIB, Level of Evidence C).

Recanalization rates and outcomes in basilar artery occlusionvary widely for both IA and IV thrombolysis, which is likely dueto the wide clinical presentation and differing mechanisms andseverity of underlying disease.59 Although occlusion of thebasilar artery accounts for only 6e10% of large vessel strokes inhumans, several meta-analyses have found that failure torecanalize an occluded basilar artery almost universally results ina poor clinical outcome.59 60 Failure of recanalization, coma atpresentation, as well as a proximal location of thrombus havebeen found to be associated with higher mortality rates.61

Recanalization rates of over 50% have been achieved with bothIA and IV thrombolysis in meta-analyses of multiple caseseries.59 62 A single large prospective registry, the Basilar ArteryInternational Cooperation Study (BASICS), found that in ananalysis of 592 patients, 38% of patients were treated >7 h afterictus either with antithrombotics, IV thrombolysis or IAtherapy. In this cohort of patients, endovascular therapy did notshow superiority over IV thrombolysis in terms of mortality ordependency, after adjusting for multiple factors such as age,stroke severity score and location of the occlusion.63 In theclinical trials of the MERCI and Penumbra thrombus removaldevices, posterior circulation occlusions were included andtreated with the same time parameters as the anterior circula-tion occlusion (up to 8 h following ictus) and were found tohave similar recanalization rates.20 21 Due to the relatively rarenature of basilar artery occlusion, the poor prognosis and thepaucity of prospective data, the rationale for aggressive treat-ment has been based largely on expert opinion, case series andmeta-analyses.64

ADJUNCTIVE THERAPYSystemic anticoagulation with heparin reduces the risk ofcatheter related embolism and augments the thrombolytic effectof some agents such as the now infrequently used r-proUK.Another rationale for antithrombotic therapy is prevention ofacute re-occlusion. These indications are counterbalanced by thepotentially increased risk of brain hemorrhage when heparin iscombined with a thrombolytic agent. There is no standardheparin regimen established for IA thrombolysis in acute stroke.Data from the MultiMERCI trial indicates that rates ofhemorrhage were not increased when heparin was used.65

PROACT-I18 reported a 27% rate of symptomatic brain hemor-rhage with a heparin regimen of 100 U/kg bolus and 1000 U/hfor 4 h used with IA r-proUK. Subsequently, a low dose heparinregimen was used in the PROACT studies (2000 U bolus and500 U/h for 4 h), which reduced the symptomatic brainhemorrhage rate to 7% in PROACT-I and to 10% in PROACT-II.19 GP IIb/IIIa inhibitors have never been studied ina randomized trial of IA thrombolysis in acute stroke but havebeen used anecdotally to treat re-occlusion and may be necessaryduring stent placement in the treatment of acute stroke,although dosing and route of administration are variable. Arandomized, dose escalation study of IV abciximab in AIS (notexceeding approved doses for coronary intervention) suggestedrelative safety up to 24 h after onset, although there were non-dose related asymptomatic intracranial hemorrhages.66 Use ofthe IIb/IIIa inhibitor abciximab for the IV treatment of acutestroke did not demonstrate either safety or efficacy comparedwith placebo in the phase III trial, Abciximab in EmergencyTreatment of Stroke Trial (AbESTT-II).67

THROMBOLYTIC AGENTSAll thrombolytic agents are plasminogen activators and convertplasminogen to its active agent plasmin. rt-PA (alteplase) and r-proUK are the best characterized in the treatment of AIS.18 19 23

Newer agents such as tenecteplase, reteplase, plasmin andmicroplasmin, and combination therapies to improve efficacy ofclot lysis (fibrinolytics and GP IIb/IIIa agents, and fibrinolyticsand direct thrombin inhibitors) remain investigational.68e70

Desmoteplase, a fibrin selective plasminogen activator, initiallythought to have promise as an IV thrombolytic, showed nobenefit over placebo in a phase III trial targeting an imagingdefined ischemic penumbra.71 Although some drugs may havedifferences in systemic effects and hemorrhagic complications, itremains unknown whether one thrombolytic agent is superiorto another in terms of revascularization of AIS. Only IV rt-PA isFDA approved for the treatment of acute stroke and allthrombolytics are off-label when administered IA.

IMAGINGImaging recommendations for treatment of acute stroke areincluded in the AHA guidelines for the early management ofadults with ischemic stroke.1 Imaging is a class I recommenda-tion and in most cases a non-contrast head CT will providesufficient information to guide emergent management decisions;the initial imaging evaluation is required to exclude the presenceof hemorrhage or other mass lesion mimicking ischemicstroke.72 There is no Class I evidence not to treat based on otherCT findings,1 although some findings have been associated withpoorer outcomes, such as the Alberta Stroke Program Early CTScore (ASPECTS), which has been shown to predict outcome inthrombolysis treated stroke patients with signs of acuteischemia on CT.73 The acquisition of vascular imaging, whether


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CT angiography or MR angiography images with concomitantperfusion imaging during acute stroke, has been shown to beachievable in a reasonable time frame (<15 min imaging time forMRI; 10 min for CT).74 75 CTangiography and MR angiographycan be useful to triage patients in terms of large vessel versussmall vessel disease and, therefore, to amend treatment options.For this reason, the availability of multimodality vascularimaging in acute stroke has been suggested as a quality metricfor a CSC.76 77 Using CT or MR perfusion to identify patientswith a mismatch of infarct core and ischemic penumbra, intheory, may allow improved patient selection and/or extensionof current treatment time windows and is currently an intensearea of research.

The Diffusion and Perfusion Imaging Evaluation for Under-standing Stroke Evolution (DEFUSE) investigators notedsignificant increased odds of achieving a favorable clinicalresponse in patients with MRI defined perfusion/diffusionmismatch treated with IV thrombolysis in the 3e6 h window.78

However, Desmoteplase in Acute Ischemic Stroke Trial II (DIAS-II), the only randomized trial using an ischemic penumbradefined by perfusion imaging to select patients for IV throm-bolysis, failed to demonstrate benefit of desmoteplase overplacebo in the 3e9 h window.71

In 2010, a technology assessment subcommittee of theAmerican Academy of Neurology concluded that there wasinsufficient evidence to support the routine use of perfusionimaging in the triage of acute stroke patients in the diagnosis ofacute stroke.79 Current evidence states that diffusion weightedimaging is superior to CT for the diagnosis of AIS and indicatesthat, in anterior circulation stroke, the initial infarct core volumeis the best predictor of response to acute stroke therapy.79

Studies designed to determine defining thresholds for futilerevascularization and poor outcome have indicated that anASPECT score of #7 and a diffusion weighted imaging coreinfarct volume of $70e100 ml are more frequently associatedwith poor clinical results.73 80e83

CONCLUSIONAIS secondary to large vessel occlusion is a potentially devas-tating disease for which best treatment remains elusive.Recanalization efficacy and safety has been shown for IAthrombolysis and some thrombectomy devices. Randomizedcontrolled trials have demonstrated clinical efficacy for IAthrombolysis in selected patients with acute middle cerebralartery occlusion. The desire to promote and popularize existingtreatment options and exciting new devices or techniques mustbe tempered by the realization that the clinical efficacy of sometreatment methods remains incompletely understood andwarrants ongoing scientific and clinical research. To promotebest possible clinical practice, the administration of interven-tional stroke treatment should remain in the hands of experi-enced stroke experts who should maximize data collection toachieve the best possible patient outcomes.

Author affiliations1Department of Radiology, University Hospitals of Cleveland, Case Western ReserveUniversity, Cleveland, Ohio, USA2Department of Radiology and Neurological Surgery, Columbia University, College ofPhysicians and Surgeons Director, Neuroendovascular Service New York Presbyterian- Columbia, Neurological Institute of New York, New York, USA3University of Cincinnati Medical Center, Cincinnati, OH, USA4Division of Neurological Surgery, Barrow Neurosurgical Associates LTD, Phoenix, AZ,USA5Department of Neurological Surgery, Stony Brook University Medical Center, StonyBrook, New York, USA6Department of Neurological Surgery, University of Kentucky, Lexington, KY, USA

7Interventional Neuroradiology, Radiology Imaging Associates, Englewood, CO, USA8Department of Neurological Surgery, UMDNJ-New Jersey Medical School, Newark, NJ,USA9Department of Radiology, Forsyth Radiological Associates, Winston Salem, NC, USA10NeuroInterventional Radiology, Massachusetts General Hospital, Boston, MA, USA11Warren Alpert School of Medicine at Brown University, Director, InterventionalNeuroradiology, Rhode Island Hospital, USA12Deparments of Neurosurgery and Neurology, Wayne State University/Detroit MedicalCenter, Detroit, MI, USA13Department of Neurological Surgery, University of Medicine and Dentistry of NewJersey, Newark, NJ, USA

Acknowledgments The authors would like to thank and acknowledge all membersof the SNIS Executive Committee for their review and endorsement of thisguidelines document.

Competing interests None.

Provenance and peer review Commissioned; not externally peer reviewed.

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Corrections

Blackham KA, Meyers PM, Abruzzo TA, et al. Endovascular therapy of acute ischemic stroke:report of the Standards of Practice Committee of the Society of NeuroInterventional Surgery.J NeuroIntervent Surg 2012;4:87e93.

The following author ’s details should read: Albuquerque FC, Barrow Neurosurgical AssociatesLTD, Phoenix, AZ, USA.

J NeuroIntervent Surg 2012:4:195. doi:10.1136/neurintsurg-2011-010243corr1

Meyers PM, Blackham KA, Abruzzo TA, Gandhi CD, Higashida RT, Hirsch JA, Hsu D,Moran CJ, Narayanan S, Prestigiacomo CJ, Tarr R. on behalf of the Society forNeuroInterventional Surgery. Society of NeuroInterventional Surgery Standards of Practice:general considerations. J NeuroIntervent Surg 2012;4:11e15. doi:10.1136/neurintsurg-2011-010180.

The following author has been added to the author list: Dr. Muhammad Shazam Hussein


Eicker S, Etminan N, Turowski B, et al. Intracranial carotid artery stent placement causesdelayed severe intracranial hemorrhage in a patient with moyamoya disease. J NeuroInterventSurg 2011;3:160e162. doi:10.1136/jnis.2010.003004.

This article was published with the incorrect doi number. The correct doi number is:doi:10.1136/jnis.2010.3004.

J NeuroIntervent Surg 2012:4:195. doi:10.1136/jnis.2010.3004

J NeuroIntervent Surg May 2012 Vol 4 No 3 195

Hemorrhagic stroke

ORIGINAL RESEARCH

Stent assisted coiling of the ruptured wide neckedintracranial aneurysm

Y M Lodi,1,2 J G Latorre,3 Z El-Zammar,3 A Swarnkar,2 E Deshaies,1,2 R D Fessler4

ABSTRACTBackground Stent assisted coiling of unruptured widenecked intracranial aneurysms require antiplatelets toprevent stent thrombosis. The effect of the loading doseof antiplatelets prior to the stent coiling procedure in anunsecured wide necked ruptured intracranial aneurysm isnot known.Objective To report any potential complicationassociated with the use of both aspirin and clopidogrel instent assisted coiling of ruptured wide neckedintracranial aneurysms.Methods Consecutive patients who underwent stentassisted coiling for ruptured wide necked intracranialaneurysm were enrolled from 2005 to 2009. Patients’demographics, including Hunt and Hess grade, Fisherscale, and location and size of aneurysms, werecollected. Complications such as rupture of aneurysm,thromboembolic events, ventriculostomy associated orsystemic hemorrhages were recorded. Additionally, a 90day outcome measurement was obtained using theGlasgow Outcome Scale.Results 22 patients with a mean age of 50613 yearsunderwent stent assisted coiling. A loading dose ofclopidogrel 300 mg and aspirin 325 mg orally were givenprior to stent placement. There was no intraoperativerupture of aneurysm, ventriculostomy associatedhemorrhage or systemic hemorrhagic event. There weretwo episodes of stent thrombosis; one was anasymptomatic event which developed during the stentassisted coiling procedure and resolved spontaneously;the other was symptomatic which required intra-arterialadministration of glycoprotein IIbIIIa receptor antagonist.There was no mortality and good outcome was observedin 82% of patients.Conclusion In our series of carefully selected patients,therapeutic dual antiplatelet loading prior to stentassisted coiling of ruptured wide necked intracranialaneurysm was not associated with increased bleedingcomplications. However, thromboembolic events remainthe main challenge. Further study is required to confirmthe safety of antiplatelet loading in stent assistedruptured intracranial aneurysm coiling.

INTRODUCTIONThe challenges of stent assisted treatment ofcomplex intracranial aneurysm have been describedin previous studies. Most of the data1e9 came fromexperiences of using Neuroform stents (BostonScientific Target, Fremont, California, USA) whichwere approved by the Food and Drug Administra-tion in 2002 under humanitarian device exemption.The Enterprise stent (Cordis Neurovascular, Miami,Florida, USA) is a relatively new intracranial stent

approved by the Food and Drug Administration in2007 under the guideline of humanitarian deviceexemption for the treatment of wide neckedintracranial aneurysm. The uses of these types ofstents have been associated with technical chal-lenges, including difficulties in navigation of stent,imprecise placement of stent and stentmigration.1e10 The technical challenge in naviga-tion of stent in the intracranial circulation variesfrom 3% to 14.2%, and the incidence of stentmigration ranges from 1% to 16%. The clinicalcomplications associated with stents includeintraoperative rupture of aneurysm and immediateor delayed thromboembolic events associated withstent.1e8 10 The most common clinical complica-tion is transient or permanent thromboembolicevent related to intracranial stent, the incidence ofwhich varies from 2% to 21%. The second mostcommon clinical complication is intraoperativerupture of aneurysm and hemorrhage that variesfrom 1.5% to 15%. Most of the patients enrolled inthe previous studies had unruptured wide neckedaneurysms and the numbers of ruptured intracra-nial aneurysm patients were very small. However,two recent studies11 12 enrolled many rupturedwide necked aneurysms but the results varied.Recently, two studies13 14 deliberately evaluated therisk and benefit of stent assisted repair of rupturedintracranial aneurysms. In both studies13 14

there was no preoperative standard antiplateletregiment using aspirin and clopidogrel for theprotection of stent. However, in one,13 glycoproteinIIbIIIa receptor antagonist was administeredintraoperatively prior to stent deployment.Currently, there is no single study that has

specifically used an antiplatelet regiment (bothaspirin and clopidogrel) prior to the deployment ofstent or evaluated the antiplatelet effect onhemorrhagic and thromboembolic complications inruptured intracranial wide necked aneurysm. Theobjective of our study was to evaluate the safety,feasibility and outcome of patients who weretreated with therapeutic doses of both aspirin andclopidogrel prior to stent assisted coiling of theirruptured intracranial aneurysm. Additionally, wetried to evaluate any hemorrhagic complicationsassociated with the use of antiplatelets and place-ment of external ventricular drainage (EVD)catheter in our series.

METHODSData of patients undergoing stent assisted treat-ment of intracranial wide necked and fusiformaneurysms were prospectively collected and

1Department of Neurosurgery,SUNY Upstate MedicalUniversity, Syracuse, New York,USA2Department of Radiology,SUNY Upstate MedicalUniversity, Syracuse, New York,USA3Department of Neurology,SUNY Upstate MedicalUniversity, Syracuse, New York,USA4Department of Neurosurgery,St John Main, Detroit,Michigan, USA

Correspondence toProfessor Y M Lodi, Departmentof Neurology, Radiology andNeurosurgery, SUNY UpstateMedical University, 750 EAdams Street, Syracuse, NY13210, USA;[email protected]

Received 28 March 2011Revised 23 May 2011Accepted 26 May 2011Published Online First18 July 2011


Hemorrhagic stroke

maintained in a database. Twenty-two consecutive patients whounderwent stent assisted coiling of an intracranial ruptured widenecked aneurysm were selected and their data were retrospec-tively analyzed. Institutional Review Board approval wasobtained prior to the treatment and retrieval of the data. Thedecision regarding surgical clipping versus endovascular stentassisted treatment of the aneurysm was made on the agreementbetween a vascular neurosurgeon and a neuroendovascularspecialist. Additionally, prior to the selection of stent assistedrepair, the treating endovascular operator thoroughly evaluatedthe architecture of the parent artery and ruled out any perceiveddifficulties in navigations through the blood vessels andcatheterizations of the aneurysm.

The clinical severity of subarachnoid hemorrhage was assessedusing the Hunt and Hess (H&H) grade, and the radiographicgrade was measured using the Fisher scale. Outcomes werepredefined on the basis of radiographic and clinical criteria.Radiographic outcomes were defined as the rate of immediateocclusion (complete occlusion (100%), near complete occlusionor neck remnant (>95% but <100%) or subtotal occlusion<95%) after stent assisted coiling of the ruptured aneurysm.Clinical outcomes were measured using the Glasgow OutcomeScale (GOS). Outcome was defined as good if the obtained GOSwas $4 at the 90 day follow-up visit.

Wide necked aneurysm was defined as having a dome to neckratio <2 or a neck >4 mm in diameter. All patients witha ruptured aneurysm who underwent stent assisted repair weretreated with both a loading dose of aspirin 325 mg and clopidogrel300 mg at least 2 h prior to intended stent deployment. Patientswere continued on both aspirin 325 mg and clopidogrel 75 mgdaily for 4 weeks after the stenting procedure and thereafter ondaily 325 mg aspirin alone.

An EVD was placed if indicated prior to the procedure andinitiation of antithrombotic medications to prevent potentialbleeding complications related to ventriculostomy insertion. Wealso avoided postprocedural intravenous anticoagulation insubarachnoid hemorrhage patients to prevent potential bleedingcomplications associated with the ventriculostomy catheter.However, standard subcutaneous anticoagulation for theprevention of deep venous thrombosis was continued.

ProceduresStent assisted coiling techniques have been described previouslyby us.7 15 16 Briefly, a 6 F guiding catheter (Boston ScientificTarget, Fremont, California, USA) flushed with continuousheparinized saline was placed in the proximal part of the vesselof interest (internal carotid, vertebral artery) and advancedthrough the guiding catheter under the guidance of fluoroscopeand roadmaps. The aneurysm was crossed with a microcatheter(SL 10; Boston Scientific Target) and a microwire (Synchro 14(Boston Scientific Target) or Transcend 14 (Cordis, Miami,Florida, USA)). The microcatheter was swapped with anexchange length microwire (X-celerator 300 cm; eV3, Irvine,California, USA). Stent delivery system was prepared andadvanced over the exchange length microwire as a unit andsubsequently deployed across the neck of the aneurysm.Recently, we had begun to use a direct approach in whicha 200 cm 0.014 compatible microwire was back loaded throughthe stent delivery system and the stent delivery system was thenadvanced as a unit through the guiding catheter. For the Enter-prise stent (Cordis Neurovascular), a 14 compatible micro-catheter (Prowler select 14; Boston Scientific Target) was loadedover the microwire (Synchro 14; Boston Scientific Target) whichwas placed on the parent artery distal to the neck of the aneu-

rysm. Placement of the microcatheter was confirmed witha microcatheter angiogram. Baseline serum activated coagulationtime was obtained, and intravenous heparin was administeredafter placement of the stent delivery catheter in the parentartery distal to the aneurysm and just 5e10 min prior to stentdelivery to achieve an activated coagulation time of 1.5 times thebaseline value. To cover the neck of the aneurysm adequately,the stent was deployed at least 4 mm proximal and 4 mm distalto the neck of the parent artery. The aneurysms in this serieswere catheterized by the direct approach in which the micro-catheter was advanced through the interstiches of the Neuro-form stent and Enterprise stent over a soft 14 compatiblemicrowire (Synchro soft 14; Boston Scientific Target). Angio-graphic and clinical follow-up was planned for each patient at 3,12, 18 and 36 months.

Statistical analysisPatient demographics, including age, race, gender, cardiovascularrisk factors, and location and size of aneurysm, were collected. AStudent’s t test of independent samples was performed tocompare means, and either a Pearson c2 test or Fisher ’s exacttest was used to compare proportions. Univariate analysis wasdone to determine if there were clinical or patient characteristicsassociated with thromboembolic complications. Due to the lownumber of observed outcomes, multivariable analysis was notperformed. All analyses were carried out using statisticalsoftware SAS V.9.1.3.

RESULTSTwenty-two patients with a mean age of 50613 years underwentsuccessful stent assisted coiling of ruptured wide necked intra-cranial aneurysms using 24 intracranial stents (Neuroform 14,Enterprise 10) (figures 1 and 2). The majority of the patients werefemale (19/22) and basilar artery bifurcation aneurysm waspresent in 11 (50%) cases. A presenting H&H clinical grade I wasobserved in 11 patients, grade II in three patients, grade III in fourpatients and grade IV in four patients. A history of hypertensionwas present in 10/22, active smoking history in 11/22 anda history of prior intracranial aneurysm was present in onepatient. In our series, antiplatelet loading with clopidogrel300 mg and aspirin 325 mg was given at least 2 h and not morethan 3 h prior to stent deployment. Fifteen patients required EVDplacementsdin 13 cases the EVD was placed at least 6 h beforethe procedure and antithrombotic loading dose while in two casesthe EVD was placed after the procedure and antithromboticloading dose, one on the same day and the other on postoperativeday 2. There was no intraoperative rupture of aneurysm orhemorrhage related to ventriculostomy placement or systemichemorrhagic events. Successful stent deployment was achieved inall cases without any significant technical difficulties.There were two episodes of stent thrombosis. The first event

was an asymptomatic non-occlusive stent thrombosis whichdeveloped during stent assisted coiling procedure in a 38-year-oldwoman (table 1, figure 3) with right paraophthalmic blisterruptured aneurysm (presenting H&H grade I and Fisher grade 3).In this case, early stent thrombosis occurred after multipleattempts were made to place the microcatheter into the aneu-rysm for suitable placement of coil. At that time it was decidedto abort further attempts to catheterize the aneurysm and themicrocatheter was withdrawn from the parent artery. Since theaneurysm was unsecured and the stent was non-occlusive withgood antegrade flow, the operator decided to observe for 45 minto see the progression of stent thrombosis instead of adminis-tering a thrombolytic drug. The patient was given additional


Hemorrhagic stroke

intravenous fluid and blood pressure was kept at the higher limitof normal. Within 20 min after withdrawal of the microcatheter,stent thrombosis began to resolve spontaneously and showedcomplete resolution in 45 min. The procedure was rescheduledin 6 days when successful placement of coil was achievedwithout any recurrent thrombosis. The patient was dischargedhome after 21 days with a GOS score of 5. The second event wasobserved on postoperative day 2 in a 46-year-old woman withH&H grade III and Fisher grade 3 who underwent stent assistedcoiling of a ruptured basilar artery bifurcation aneurysm.Emergent intra-arterial administration of glycoprotein IIbIIIareceptor antagonist resulted in complete resolution of clot andsymptoms. There was no mortality in our series. Good outcomewas observed in 82% of patients (GOS score of 5 in 17 and GOS4 in one) and poor outcome in 18% of patients (GOS 3 in four).

DISCUSSIONStent assisted coiling of ruptured wide necked intracranialaneurysm patients has been included in the series of stentassisted coiling of intracranial aneurysms11 12 and the resultshave been conflicting. In a recent study of 40 patients with 41acute ruptured aneurysms treated with 41 Neuroform stents, anintraoperative intravenous dose of glycoprotein IIbIIIa receptorantagonist (eptifibatide) was given intravenously during the

procedure instead of oral antiplatelets prior to stent placement.13

However, a postoperative loading dose of clopidogrel and aspirinwas provided. Intraoperative rupture of aneurysm was reportedin 3/41 aneurysms while non-aneurysmal intracranial hemor-rhage was observed in 2/40 cases. An intraoperative radiographicthromboembolic event was observed in four cases, three ofwhich resolved after administration of eptifibatide. Ischemicstroke was observed in 5/40 cases, one immediate and four ina delayed fashioned. In another study,14 61 patients with acutelyruptured intracranial aneurysm were treated with stent assistedcoiling. Most patients received intraprocedure acetylsalicylicacid. Some received heparin before stent deployment and somereceived heparin after stent deployment. Most received bothaspirin and clopidogrel after the procedure. Technical successwas observed in 72%. Intraoperative rupture of aneurysm wasobserved in 4/61 cases. Intraoperative thromboembolic eventsoccurred in 9/61 cases. Mortality was observed in 20%. Goodoutcome was observed (GOS 5 and 4) in 69% of cases.In comparing the results of our study with the most recent

studies13 14 (table 2), reporting only ruptured aneurysms, weobserved no intraoperative rupture or postoperative hemor-rhages in our series. In addition, compared with our series, thethromboembolic events, including stroke, were also higherin previous series,13 14 including a study13 that utilized

Figure 2 (A) A 42-year-old womenpresented with a subarachnoidhemorrhage Hunt and Hess grade I andFisher grade 1 due to a ruptured basilarartery bifurcation complex aneurysm.(B) Patient underwent stent assistedrepair in the acute phase withobliteration of the aneurysm.

Figure 1 (A) A 49-year-old womenwith multiple cerebrovascular riskfactors presented with subarachnoidhemorrhage Hunt and Hess grade IVand Fisher grade 3 due to a rupturedbasilar artery (BA) bifurcationaneurysm. (B) Patient underwent stentassisted repair of the aneurysm in theacute phase.


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Table 1 Clinical characteristics and outcome of patients who underwent stent assisted repair of ruptured wide necked intracranial aneurysms

Age/sex H&H FisherLocation ofaneurysm Size (mm)

Time of EVDplacement Stent

Stentthrombosis

Immediate resultof obliteration

12 monthsresults

30 and 90day GOS

71/M I 1 BA bifurcation 9 No Enterprise No Near complete Pending 5

39/F III 4 Left VA 4.4 After Neuroform No Near complete Complete 5

59/F IV 1 Left paraclinoid ICA 5 After Neuroform No Subtotal Complete 5

48/F III 4 BA bifurcation 9 Before Neuroform No Subtotal Complete 3

53/M IV 4 Right MCA 13 Before Neuroform No Subtotal Complete 5

42/F I 1 Left ophthalmic artery 6 No Neuroform No Subtotal Near complete 5

51/F IV 4 BA bifurcation 6 before Enterprise No Near complete Pending 5

34/F III 2 Right PICA 5 Before Enterprise No Complete Complete 5

38/F I 1 Left ophthalmic artery 3 No Enterprise Yes Complete Complete 5

31/F III 4 BA bifurcation 7 No Enterprise No Complete Complete 3

30/F I 1 BA bifurcation 4 No Enterprise No Complete Complete 5

67/M III 4 BA bifurcation 16 Before Enterprise No Subtotal Subtotal 4

42/F I 2 PComA 5 Before Neuroform No Subtotal Complete 5

33/F I 4 PComA 8 Before Neuroform No Subtotal Near complete 3

67/F II 2 MCA 30 Before Neuroform No Subtotal Subtotal 5

68/F III 4 BA bifurcation 29 Before Neuroform No Subtotal Complete 3

52/F I 2 PComA 6 Before Neuroform No Complete Complete 5

46/F III 3 BA bifurcation 9 Before Neuroform Yes Near complete Complete 5

36/F II 2 BA bifurcation 7 Before Neuroform No Complete Complete 5

57/F I 2 BA bifurcation 8 No Neuroform No Subtotal Near complete 5

37/F I 2 PComA 9 Before Neuroform No Near Complete Complete 5

59/F I 2 BA bifurcation 15 No Enterprise No Subtotal Near Complete 5

After, after endovascular procedure; Before, before endovascular procedure; BA, basilar artery; EVD, extraventricular drainage; GOS, Glasgow Outcome Scale (GOS 5, independent with nosymptoms; GOS 1, dead); H&H, Hunt and Hess grade; ICA, internal carotid artery; MCA, middle cerebral artery; PComA, posterior communication artery; PICA, posterior inferior cerebellarartery; VA, vertebral artery.

Figure 3 (A) A 38-year-old women presented with subarachnoid hemorrhage Hunt and Hess grade I and Fisher grade 1 due to a ruptured leftophthalmic internal carotid artery (ICA) aneurysm and planned to undergo stent assisted repair. A second aneurysm at the cavernous ICA was alsodiscovered. (B) Later view angiogram of the left ICA demonstrated asymptomatic non-occlusive stent thrombosis in the ophthalmic and cavernousportions of the left ICA. (C) Lateral view angiogram of the left ICA demonstrates progressive resolution of stent thrombosis in the ophthalmic andcavernous ICA. (D) Patient underwent repeat procedure with placement of a second stent and successful coiling of the aneurysm. (E) Lateral viewangiogram of the left ICA demonstrated successful coiling of the aneurysms.


Hemorrhagic stroke

glycoprotein IIbIIIa receptor antagonist prior to stent deploy-ment. These observations may be due to the differences in thepharmacological properties of antiplatelet agents used duringstent assisted coiling of ruptured aneurysm.The suspected mechanisms of intraoperative rupture of

aneurysm during coiling including factors associated with themicrowire, microcatheter or coils, have been described previ-ously.7 When a ruptured aneurysm stops bleeding, we suspectthat the hemostatic process has begun successfully by activationof platelets and formation of thrombus. After a few hours, theconcentration of platelet in the thrombus increases, making thethrombus rich in platelets. Based on their pharmacologicalproperties, the use of glycoprotein IIbIIIa receptor antagonists inunsecured aneurysms may promote breakdown of dihydrogensulfate bondage between platelets, leading to the lysis of plateletrich clot/thrombus which then increases the chance of intra-operative rupture. Since both aspirin and clopidrogel have noeffect on pre-existing clot or platelet rich thrombus, theoreticallythey will not increase the chance of aneurysm rupture orhemorrhage. However, in the event of aneurysm rupture orhemorrhage, both aspirin and clopidogrel may increase theseverity of hemorrhages. We have not compared aspirin andclopidogrel with glycoprotein IIbIIIa receptor antagonists so weare unable to determine whether the combination of aspirin andclopidogrel has any clinical advantage over glycoprotein IIbIIIareceptor antagonists or vice versa.Our study and other recently published series13 14 (table 2)

revealed that the incidence of thromboembolism is higher inruptured series than in unruptured series.7 12 15 The possiblemechanism of higher rate of thromboembolism in the rupturedseries, including our series, may be due to the fact that most ofour patients received antiplatelet load just 2 h prior to theprocedure and therefore therapeutic platelet inhibition mightnot have been achieved prior to stent placement. Based ona previous study,17 a loading dose of clopidogrel provides plateletinhibition of 55% in 1 h and 80% within 5 h of administration.Therefore, loading doses can be administered earlier prior tostent placement which may potentially reduce intraoperativethromboembolic events. Additionally, a bedside platelet aggre-gations assay can be performed for all patients just before stentplacement to identify those patients who have poor plateletinhibition. For the prevention of postoperative thromboembolicevents, a second loading dose of antiplatelet may be adminis-tered if a platelet inhibition assay performed postprocedureindicates poor platelet inhibition.Our study has several limitations. Firstly, the small size of our

series may be insufficient to capture the true incidence ofbleeding complications of periprocedural regimens of dual anti-platelets and intraoperative intravenous heparin that we used inour cohort of patients treated for ruptured wide neck intracra-nial aneurysm. Secondly, in our series we did not use a balloonassisted technique in which some of these aneurysms couldhypothetically have been repaired. Thirdly, the retrospective,single arm and open label design of our study may limit itsexternal validity. However, what we report here is a pilot studyexamining mainly the safety, feasibility and outcome of the dualantiplatelet regimen that we used in our patients cohort.In conclusion, in carefully selected cases, stent assisted coiling

of ruptured wide necked intracranial aneurysm using preproce-dural aspirin and clopidogrel loading is feasible and not associ-ated with increased bleeding complications. Ventriculostomyrelated complications could be avoided if the ventriculostomy isperformed at least 6 h prior to the antiplatelet loading dose.However, the thromboembolic events remain the main challengeTa

ble2

Com

parison

ofthecurrentstudywith

previous

studiesthat

treatedruptured

widenecked

aneurysm

susingstent

Study

Noof

patients

Antiplateletregimen

Intraoperative

rupture(n

(%))

Intracerebral

hemorrhage(n

(%))

Thromboem

bolic

event

Stroke

EVDrelated

complications

Outcome

Jankow

itz13

41Intraoperativeglycoprotein

IIbIIIaantagonist

followed

bypostoperativeaspirin

and

clopidogrel.Standarduseof

heparin

duringprocedurewas

maintained

3(4.5)

2(5)

Total¼9(10%

)Intraoperative¼

4(3

resolved

and1resultedin

stroke)

Delayed

in5

5with

good

outcom

eTotalevents

¼9catheter

trackpunctuate

hemorrhage¼7

(3clinicallysignificant),

Largehemorrhage¼2

(sym

ptom

aticin

1)

Described

asgood,but

noclearspecification

was

provided

Thantinen

14

61Nostandard

antiplateletregimen.

Som

ereceived

intraoperative

acetylsalicylateandsome

received

intraoperativeheparin

followed

byaspirin

and

clopidogrel

4(7)

Totalevents¼7

(11%

)Not

described

Not

described

Mortality20%.Goodoutcom

ein

69%(GOS5and4)

Lodi

(current

study)

22Loadingdose

of300mgclopidogrel

andaspirin

atleast2hpriorto

stent

placem

entfollowed

by75

mgof

clopidogreland325mgaspirin

daily

for4weeks.Allpatientsreceived

intravenousheparin

toobtain

anactivated

coagulationtim

eof

1.5e

2tim

esbaselinepriorto

stent

deployment.

00

Totalevents¼2

Intraoperativenon-occlusivestent

thrombosis,

1of

which

resolved

spontaneously.

Delayed

symptom

atic

in1requiredintra-arterial

administrationof

GPIIbIIIareceptor

antagonist

which

resultedin

completeresolution

00

Nomortality.

Goodoutcom

e82%(GOS5in

17,GOS

4in

1).Poor

outcom

e18%

(GOS3in

4)

EVD,extraventricular

drainage;GOS,Glasgow

OutcomeScale.


Hemorrhagic stroke

in stent assisted coiling of ruptured intracranial wide neckedaneurysm. Therefore, standard antiplatelet regimens should notbe withheld prior to stent assisted coiling of carefully selectedruptured wide necked aneurysms. A larger prospective andblinded study looking at the same outcomes in a similar cohortis needed to replicate and confirm our results.

Competing interests None.

Ethics approval Institutional Review Board approval was obtained.

Provenance and peer review Not commissioned; externally peer reviewed.

REFERENCES1. Fiorella D, Albuquerque FC, Han P, et al. Preliminary experience using the Neuroform

stent for the treatment of cerebral aneurysms. Neurosurgery 2004;54:6e16.2. Benitez RP, Silva MT, Klem J, et al. Endovascular occlusion of wide-necked

aneurysms with a new intracranial microstent (Neuroform) and detachable coils.Neurosurgery 2004;54:1359e67.

3. dos Santos Souza MP, Agid R, Willinsky RA, et al. Microstent-assisted coiling forwide-necked intracranial aneurysms. Can J Neurol Sci 2005;32:71e81.

4. Lylyk P, Ferrario A, Pasbon B, et al. Buenos Aires experience with the Neuroformself-expanding stent for the treatment of intracranial aneurysms. J Neurosurg2005;102:235e41.

5. Fiorella D, Albuquerque FC, Deshmukh VR, et al. Usefulness of the Neuroform stentfor the treatment of cerebral aneurysms: results at initial (3-6-mo) follow-up.Neurosurgery 2005;56:1191e201.

6. Biondi A, Janardhan V, Katz JM, et al. Neuroform stent-assisted coil embolization ofwide-neck intracranial aneurysms: strategies in stent deployment and midtermfollow-up. Neurosurgery 2007;61:460e8.

7. Yahia AM, Gordon V, Whapham J, et al. Complications of Neuroform stent inendovascular treatment of intracranial aneurysms. Neurocrit Care 2008;8:19e30.

8. Sani S, Jobe KW, Lopes DK. Treatment of wide-necked cerebral aneurysmswith the Neuroform2 Treo stent. A prospective 6-month study. Neurosurg Focus2005;18:E4.

9. Wanke I, Doerfler A, Schoch B, et al. Treatment of wide-necked intracranialaneurysms with a self-expanding stent system: initial clinical experience. AJNR Am JNeuroradiol 2003;24:1192e9.

10. Katsaridis V, Papagiannaki C, Violaris C. Embolization of acutely ruptured andunruptured wide-necked cerebral aneurysms using the neuroform2 stent withoutpretreatment with antiplatelets: a single center experience. AJNR Am J Neuroradiol2006;27:1123e8.

11. Mordasini P, Walser A, Gralla J, et al. Stent placement in the endovasculartreatment of intracranial aneurysms. Swiss Med Wkly 2008;138:646e54.

12. Mocco J, Hanel RA, Sharma J, et al. Use of a vascular reconstruction device tosalvage acute ischemic occlusions refractory to traditional endovascularrecanalization methods. J Neurosurg 2010;112:557e62.

13. Jankowitz B, Thomas AJ, Vora N, et al. Risk of hemorrhage in combined Neuroformstenting and coil embolization of acutely ruptured intracranial aneurysms. IntervNeuroradiol 2008;14:385e96.

14. Tahtinen OI, Vanninen RL, Manninen HI, et al. Wide-necked intracranial aneurysms:treatment with stent-assisted coil embolization during acute (<72 hours)subarachnoid hemorrhagedexperience in 61 consecutive patients. Radiology2009;253:199e208.

15. Yahia AM, Latorre J, Gordon V, et al. Thromboembolic events associated withneuroform stent in endovascular treatment of intracranial aneurysms.J Neuroimaging 2010;20:113e17.

16. Yahia AM, Gordon V, Whapham J, et al. Sapphire platinum detachable coilexperience in a tertiary-care facility. Neurocrit Care 2007;7:128e35.

17. Moshfegh K, Redondo M, Julmy F, et al. Antiplatelet effects of clopidogrelcompared with aspirin after myocardial infarction: enhanced inhibitory effects ofcombination therapy. J Am Coll Cardiol 2000;36:699e705.

Correction

K A Blackham, P M Meyers, T A Abruzzo, et al. Endovascular therapy of acute ischemicstroke: report of the Standards of Practice Committee of the Society of NeuroInterventionalSurgery. J NeuroIntervent Surg 2012;4:287e93.

The author name F C Alberquerque should have been spelt FC Albuquerque.Muhammad Shazam Hussain was missing from the author list. The list now reads:

K A Blackham, P M Meyers, T A Abruzzo, F C Albuquerque, D Fiorella, J Fraser, D Frei,C D Gandhi, D V Heck, J A Hirsch, D P Hsu, M Shazam Hussain, M Jayaraman, S Narayanan,C Prestigiacomo, J L Sunshine, on behalf of the Society for NeuroInterventional Surgery.


286 J NeuroIntervent Surg July 2012 Vol 4 No 4

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Endovascular therapy of acute ischemic stroke: report of the … · Endovascular therapy of acute ischemic stroke: report of the Standards of Practice Committee of the Society of